Netrin-1-Dependent Spinal Interneuron Subtypes Are Required for the Formation of Left-Right Alternating Locomotor Circuitry

Rabe, Nadine; Gezelius, Henrik; Vallstedt, Anna; Memic, Fatima; Kullander, Klas

doi:10.1523/jneurosci.5096-09.2009

Cited by 78 publications

(90 citation statements)

References 39 publications

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“…Interestingly, in a hypomorphic DCC mutant, the 'kanga' mice, the CST projects bilaterally and hindlimbs move synchronously, which would support the current model [58]. However, in isolated spinal cord preparations, there is also a significant reduction of commissural projections from spinal cord CINs in DCC and Netrin-1 knockout mice, which could also account for the observed locomotor deficits [59,60] ( Figure 3B).…”

Section: Genetic Alteration Of Axonal Laterality Impairs Locomotionsupporting

confidence: 68%

Development and plasticity of commissural circuits: from locomotion to brain repair

Chédotal

2014

Trends in Neurosciences

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Section: Genetic Alteration Of Axonal Laterality Impairs Locomotionsupporting

confidence: 68%

Development and plasticity of commissural circuits: from locomotion to brain repair

Chédotal

2014

Trends in Neurosciences

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“…2 and Supplementary Fig. 2) [23][24][25][26]34,35 . Boc mutant embryos were similar to WT with a relatively mild (B5% previously reported widening) commissural defasciculation phenotype (Fig.…”

Section: Ventral Neuron Position Is Correlated With Commissural Axonsmentioning

confidence: 99%

Commissural axonal corridors instruct neuronal migration in the mouse spinal cord

et al. 2015

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Unravelling how neurons are guided during vertebrate embryonic development has wide implications for understanding the assembly of the nervous system. During embryogenesis, migration of neuronal cell bodies and axons occurs simultaneously, but to what degree they influence each other's development remains obscure. We show here that within the mouse embryonic spinal cord, commissural axons bisect, delimit or preconfigure ventral interneuron cell body position. Furthermore, genetic disruption of commissural axons results in abnormal ventral interneuron cell body positioning. These data suggest that commissural axonal fascicles instruct cell body position by acting either as border landmarks (axon-restricted migration), which to our knowledge has not been previously addressed, or acting as cellular guides. This study in the developing spinal cord highlights an important function for the interaction of cell bodies and axons, and provides a conceptual proof of principle that is likely to have overarching implications for the development of neuronal architecture.

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“…Disruption of one netrin allele, or of its UNC5H receptors, is lethal during early embryogenesis in mice, suggesting a crucial role for netrin-1 and its UNC5H receptors in this process (Navankasattusas et al, 2008;Rabe et al, 2009). As was mentioned above, netrin-1 and UNC5B have been shown to control angiogenesis and vasculogenesis, two essential processes for a successful placentation during the first trimester of pregnancy.…”

Section: B C Amentioning

confidence: 89%

Hypoxia-inducible factor 1 controls the expression of the uncoordinated-5-B receptor, but not of Netrin-1, in first trimester human placenta

Dakouane-Giudicelli¹,

Alfaidy²,

Bayle³

et al. 2011

Int. J. Dev. Biol.

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Uncoordinated-5 homologs 1-4 (UNC5H1-4) transmembrane netrin receptors are reported to control a number of cellular processes, including axonal guidance, angiogenesis and cell proliferation. These receptors are known as "dependence receptors" because they are able to induce apoptosis in the absence of their ligand, netrin. We have recently reported the localization of netrin-1 and its uncoordinated-5-B (UNC5B) receptor in both villous and extravillous cytotrophoblasts in the human placenta. However, the roles that netrin-1 and UNC5B play in the development of the placenta, as well as the regulation of their expression during the early stages of placental development, remain unexplored. Placental explants were used to demonstrate a proliferative effect of netrin-1 on cytotrophoblasts, as assessed by Ki67 staining. Primary cytotrophoblasts collected at different gestational ages during the first trimester of pregnancy indicated that netrin-1 mRNA expression decreased after 6 weeks of gestation (wg), whereas UNC5B expression increased gradually up to 13-14 wg. The BeWo cell line was used to evaluate the effect of hypoxia on the expression of netrin-1 and UNC5B. Primary cytotrophoblast and BeWo cells cultured under hypoxic conditions exhibited a decrease in the expression of UNC5B both at the mRNA and protein levels; in contrast, hypoxia induced no change in the levels of netrin-1. When hypoxia-inducible factor 1a (HIF-1a) was knocked down by siRNA, we found a significant increase in UNC5B expression, indicating that the HIF-1 pathway is involved in hypoxia-induced UNC5B transcriptional down-regulation. Altogether, these results demonstrate the role of netrin-1 as a new mitogenic factor for cytotrophoblastic cells, report the pattern of expression of netrin-1 and its receptor, UNC5B, in the human placenta during the first trimester of pregnancy, and bring insights into the direct control of the expression of UNC5B by HIF-1. KEY WORDS: human placenta, hypoxia, UNC5B, Netrin and netrin receptors are widely expressed in various mammalian embryonic and adult tissues (Engelkamp 2002). These proteins are reported to control a number of cellular processes such as axonal guidance, angiogenesis, morphogenesis, proliferation and apoptosis (Cirulli and Yebra 2007;Llambi et al., 2001; Matilanien et al., 2007). Netrin-1 has been proposed to play a role in tumorigenesis through the regulation of apoptosis. This survival activity is mediated via the inhibition of netrin-1 dependence receptors DCC (Deleted in Colorectal Cancer) and UNC5H Abbreviations used in this paper: DCC, deleted in colorectal cancer; HIF, hypoxiainducible factor; siRNA, small interfering RNA; UNC5B, uncoordinated-5-B; UNC5H, uncoordinated-5-homolog; wg, weeks of gestation.(uncoordinated-5-homolog).Of all the proteins in the netrin and UNC5 families, netrin-1 and UNC5B are the most extensively studied. We have recently characterized the expression of netrin-1 and its UNC5B receptor in the human placenta during the first and last trimesters of 982 M. D...

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Netrin-1-Dependent Spinal Interneuron Subtypes Are Required for the Formation of Left-Right Alternating Locomotor Circuitry

Cited by 78 publications

References 39 publications

Development and plasticity of commissural circuits: from locomotion to brain repair

Development and plasticity of commissural circuits: from locomotion to brain repair

Commissural axonal corridors instruct neuronal migration in the mouse spinal cord

Hypoxia-inducible factor 1 controls the expression of the uncoordinated-5-B receptor, but not of Netrin-1, in first trimester human placenta

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